Vulvodynia is a poorly understood and treated chronic pain disorder that affects an estimated 14 million women and is characterized by significant variation in location, temporal characteristics and clinical course. The contribution o multiple known and unknown components hinders adequate diagnosis and consequently rational choice of treatment. Identification and assessment of these underlying mechanisms would greatly advance the phenotyping of this prevalent disorder, which is a necessary step towards efficacious treatment. The proposed methods contain three necessary components. The first provides a systemic clinical exam of vulvar mucosa and muscle that is broadened greatly to include consideration of pain processes that are initiated by persistent pain. These include spinally-mediated C-fiber temporal summation, central sensitization and altered pain regulatory mechanisms that include decreased descending inhibition and increased descending facilitation. The methods will also evaluate a general pain amplification mechanism that has been observed in vulvodynia, fibromyalgia and low back pain, and that is likely distinct from spinally-mediated central sensitization. The second component recognizes the influence of psychological variables that determine distinct subgroups in other disorders and that can influence pain through physiological mechanisms ranging from increased muscle tension to increased sympathetic outflow. The proposal will use our previous experience and current results from a large-scale multi-center study (n=3500) and from an ongoing program project (n=1500) to evaluate important dimensions of psychological distress and cognitive style. The third component recognizes that adequate analysis of multiple evaluation procedures requires considerable knowledge and expertise in advance statistical methods. The research team includes a statistician, Dr. Eric Bair, who is especially knowledgeable about these types of analyses and experiences including the multi-center study and the program project cited above. The research team is particularly well prepared to conduct the proposed investigation because of significant experience and expertise in the proposed methods including clinical assessment and treatment of vulvodynia, psychophysical and neurophysiological assessment of pain and sensory function and sophisticated statistical analysis of data from pain assessments. The proposed work is supported by a significant amount of pertinent preliminary data that includes advanced clinical and psychophysical methodology. PUBLIC HEALTH RELEVANCE: Vulvodynia is a disabling chronic pain condition that affects 14 million women in the USA at some point in their lifetime. Little is known about the underlying mechanism and effective treatment of women with vulvodynia. Our team is very experienced in the analysis of complex pain mechanisms and is developing novel tools and classification algorithms to identify the relative contribution of multiple pain mechanisms in individual patients to enhance diagnosis and choice of tailored, mechanistic-based treatments.